6,8‐Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53

• Published in: Environmental toxicology 2021-05, Vol.36 (5), p.914-925
• Main Authors: Choi, Yong Jun, Lee, Jongsung, Ha, Sang Hoon, Lee, Han Ki, Lim, Heui Min, Yu, Seon‐Hak, Lee, Chang Min, Nam, Myeong Jin, Yang, Yung‐Hun, Park, Kyungmoon, Choi, Youn Soo, Jang, Kyu Yun, Park, See‐Hyoung
• Format: Article
• Language: English
• Subjects: 6,8‐diprenylorobol; Acetylcysteine; AKT protein; Apoptosis; Cancer; Cell activation; Cell Line, Tumor; Cell proliferation; Cell Survival; Cell viability; Cells; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colorectal cancer; DNA; DNA fragmentation; Humans; Incubation period; Intracellular; Kinases; Medical sciences; Oxygen; p53; p53 Protein; Phosphorylation; Proliferation; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tumor Suppressor Protein p53
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23093

6,8‐Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8‐diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8‐diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8‐Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose‐ and time‐dependent manner. A 40 μM of 6,8‐diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8‐diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8‐diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen‐activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8‐diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N‐acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8‐diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8‐diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8‐diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS.